Ocular effects of drugs are easily indexed, noninvasive measures of drug action. In these studies the effects of several classes of abused drugs are measured on the size of the eye, the response to light flashes or prolonged light stimuli and the ability of the eye to track moving targets. These effects are correlated with performance and subjective effects to evaluate the utility of ocular measures for drug detection and fitness for duty applications. Methods: In a series of experiments the effects of ambient light, circadian factors between and within subject variability on dynamic pupillary responses was measured. In other experiments the effects of ethanol, pentobarbital, marijuana, cocaine, opiates and amphetamines were studied. Dependent measures included: subjective effects (drug liking, ARCI subscales, visual analog scales); physiologic measures (pupillary measures: size, constriction and dilation velocities, latency, tracking, accommodate changes); performance (circular lights, card sorting, rotary pursuit, rapid math, DSST, letter search). Studies were double-blind placebocontrolled, within subject crossover design. Results: on pupillary and ocular measures, the between subject variability is large but the within subject variability is small. The study drugs typically causes significant effects on the dependent measures of the study. The effects were significant as a function of drug dose and the time after administration. The ocular changes occurred at the peak of subjective effect and performance impairment. Response discrepancy was evident in that subjects with the largest pupillary effects did not consistently demonstrate the greatest subjective or performance effects. Significance: These results indicate that baseline (controlled) data must be collected from individuals before pupillometry can be used to determine drug impairment. The small within subject variability suggests that pupillary measures may be used as a rapid screening for populations where the baseline is known.